Kawasaki disease (KD) is an emerging third world pediatric disease that frequently leaves lasting coronary abnormalities. Current treatment is intravenous (IV) immunoglobulin (Ig) (or IVIG, or IvIG) infusion, which is expensive and requires hospitalization and often not an option in the third world regions where the disease is prevalent.
IVIG therapy generates a specific population of natural regulatory T cells (nTregs) that recognize the heavy region constant (Fc) of immunoglobulin G. Fc-specific Treg are very relevant to maintain vascular homeostasis and can be found in Kawasaki disease subjects that do not develop arterial abnormalities after IVIG and in a variety of acute pediatric febrile controls but not autoimmune diseases. Normal healthy adults have detectable Fc-specific nTreg in their peripheral blood suggesting that this Treg repertoire is important in controlling vascular homeostasis.
Children that develop coronary arteries abnormalities despite IVIG treatment do not expand Fc-specific nTreg. Characterization of Fc-specific nTreg clones derived from children that did not develop arterial abnormalities after KD suggest that the suppression mechanism of pro-inflammatory T cell responses (by Fc-specific nTreg) occur in the lymph nodes, and Fc-specific nTregs are activated by resident B cells. IgG+ mature B cells can activate Fc-specific nTreg in the absence of soluble Fc fragments. The characterization of immunodominant Fc peptides that bind multiple Human Leukocytes Antigens (HLA) alleles would be a great alternative to IVIG.